Salts of esters of para-hydroxybenzoic acid



Patented Got. 6, 1936 UNITED. STATES 2,056,176 SALTS or ESTERS-OFPARA-HYDROXY- BENZOIG ACID William H. Engels and John Weijlard, RahwayN. J., assignors to Merck & 00., Inc., Rah-way, N. J., a corporation ofNew Jersey No Drawing. Original applicationJune 17, 1933, Serial No.676,322. Divided and this application September 19, 1935, Serial No.41,273

2 Claims. (01. 260-104l This is a division of our co-pendingapplication,

SerialNo. 676,322. I

The present invention relates to the production of salts of esters ofpara-hydroxybenz oic acid useful for preserving foods and beverages andas antiseptics. Thegeneral' object is to provide a series of suchcompounds having superior physical and chemical properties which adaptthem for food preservatives, especially in solutions of a neutral oralkaline character. A further object is to provide such salts in theform of dry, nonhygroscopic powders, which renders them more eflicientfor practical industrial employment. Further objects and applicationswill become apparent from the further disclosures herein.

Sodium benzoate has long been employed as a chemical preservative agentfor foodstuffs, but its use has been limited due to its ineffectivenessin neutral or alkaline media. It has been established, however, thatesters of para-hydroxybenzoic acid, while being relatively non-toxic,exert powerful inhibiting action against bacteria, fungi, etc., even inneutral and alkaline solutions, and the use of such esters has beenhighly recommended for the requirements of the food industry, wheresodium benzoate had become worthless on account of the neutral oralkaline reaction of the media.

The esters of para-hydroxybenzoic acid, as far as their usefulness inthe industries is concerned, have one common fault, namely, their lowand slow rate of solubility in water. These esters, however, readilydissolve in solutions of the alkali metal hydroxides forming solutionsof the phenolic sodium salts of the esters. It has been attempted toform these salts also in the dry state for ease of distribution andapplication. However, the extremely hygroscopic nature of these alkalimetal salts has prevented their manufacture in the pure state; and,therefore, the alkali metal salts of such esters found on the market arereally mixtures of powdered sodium hydroxide and the esters,particularly the methyl and propyl esters, as can easily be demonstratedby treating these mixtures with anhydrous ether, by which only theesters are dissolved, the alkali metal hydroxide remaining behind. It isevident that such mixtures cannot remain stable very long in thepresence of moist air or carbon dioxide.

A further drawback of such mixtures of alkali metal hydroxide and thenamed esters, is that the esters themselves will dissolve in water or inaqueous media only when used in relatively high concentrations of thehydroxide-ester mixture.

When the mixtures are used in solutions of sufllciently lowconcentrations to which they must be limited, whenemployed in apractical way for the inhibition of the growth of bacteria or fungi infoodstuffs, the alkali metal hydroxide dissolves out rapidly and the pHof the solution which results, comprising the hydroxide in water, is notsufficiently alkaline to freely dissolve the ester in effective amount.In such weakly alkaline hydroxide solutions the esters do not go intosolution any faster than they would if only pure water were used. Inorder to get sufficient inhibiting effect from the esters contained insuch mixtures the amount thereof necessary to be used would go beyondpermissible limits.

It has now been found by us that, while the alkali metal salts are toounstable for commercial production because of their hygroscopicity, thealkaline earth metal salts form dry non-hygroscopic powders and are thusavailable for convenient commercial production and use, and they havebeen found to be generally sufliciently soluble to serve as elficientchemical agents to prevent fermentation.

For practical application, the salts of calcium and magnesium have beenfound to be the most convenient, economical and eflicient. Among theesters of para-hydroxybenzoic acid which have been found especiallyeflicient as preservatives are the ethyl, n-propyl, 'iso-propyl,n-butyl, iso-butyl, iso-amyl and benzyl esters.

The calcium and magnesium salts of this group of esters form white,crystalline, non-hygroscopic powders. Of these new salts, those formedof the n-butyl and ethyl esters appear to be preeminently adaptable forthe purposes of their principal intended use on account of their relaatively lower toxicity, relatively greater efliciency and amplesolubility.

Thus the water solubility of the calcium salt ofn-butyl-para-hydroxybenzoic acid is about 1:125, that of the magnesiumsalt is about 1:110, whereas the approximate amounts necessary forpreservative use is about 1 part in 2000, more or less, according to themedium with which they are to be incorporated.

The barium and strontium salts of the esters can also be prepared andbehave in a similar way. These, of course, on-account of the toxicproperties of the barium and strontium salts, should not be used in thefood industries. But, in other fields of the technical industries, theywill find special applications, and they should, therefore,

be considered equivalents of the calcium and magnesium salts for thepurposes of this invention.

Convenient and preferred methods of making the various alkali earthsalts of the esters of para-hydroxybenzoic acids contemplated herein areset forth by way of illustration. Obviously, various of the severalsteps described may be modified as to quantitative relations, temperature, strength of solutions, etc., within practical limits, withoutdeparting from the scope and spirit of the present invention.

Example I.Five kg. para-hydroxybenzoic acid normal butyl ester aredissolved in 20 liters of water containing 1.03 kg. sodium hydroxide. Tothis is added a solution of 1.43 kg. anhydrous calcium chloride in 10liters of water. After mixing, the batch is allowed to stand at roomtemperature for 24 hours. The calcium salt of the parahydroxybenzoicacid butyl ester is filtered ofi,

washed and dried at to C. in the usual manner. About 5.15 kg. of the drysalt is obtained.

Example II .-Five kg. para-hydroxybenzoic acid benzyl ester aredissolved in 25 liters of water containing 0.88 kg. sodium hydroxide. Tothis is added a solution containing 2.7 kg. of MgSOi-7H2O in 10 litersof water. After mixing, the batch is allowed to stand over night. Themagnesium salt of para-hydroxybenzoic acid benzyl ester is filtered off,Washed and dried at 60 to 70 C. in the usual manner. The yield isapproximately 4.88 kg.

From the examples set iorth above by way of illustration, the chemistskilled in the art may readily produce the analogous calcium, magnesiumand other alkaline earth metal salts of any desired alkyl or aryl estersof para-hydroxybenzoic acid of the types described above, byappropriately adapting the quantitative relations stoichiometrically.

We claim as new:

1. Alkali-earth metal salts of aralkyl esters of para-hydroxybenzoicacid, forming white, nonhygroscopic crystalline powders moderatelysoluble in water and stably soluble in solutions of neutral and alkalinereaction.

2. Alkali-earth metal salts of para-hydroxybenzoic acid benzyl ester,forming white, nonhygroscopic crystalline powders, moderately soluble inwater.

WILLIAM H. ENGELS. JOHN WEIJLARD.

